Top ten most accessed articles in February

This month sees the following articles in MedChemComm that are in the top ten most accessed:

Investigation of the effect of molecular properties on the binding kinetics of a ligand to its biological target
Duncan C. Miller, Graham Lunn, Peter Jones, Yogesh Sabnis, Nichola L. Davies and Paul Driscoll
Med. Chem. Commun., 2012, 3, 449-452
DOI: 10.1039/C2MD00270A

Epigenetics—an emerging and highly promising source of new drug targets
Nessa Carey
Med. Chem. Commun., 2012, 3, 162-166
DOI: 10.1039/C1MD00264C

Minisci reactions: Versatile CH-functionalizations for medicinal chemists
Matthew A. J. Duncton
Med. Chem. Commun., 2011, 2, 1135-1161
DOI: 10.1039/C1MD00134E

Inhibition of bromodomain-mediated protein–protein interactions as a novel therapeutic strategy
Silviya D. Furdas, Luca Carlino, Wolfgang Sippl and Manfred Jung
Med. Chem. Commun., 2012, 3, 123-134
DOI: 10.1039/C1MD00201E

Development of second generation epigenetic agents
Philip Jones
Med. Chem. Commun., 2012, 3, 135-161
DOI: 10.1039/C1MD00199J

Rhodanine carboxylic acids as novel inhibitors of histone acetyltransferases
Silviya D. Furdas, Suhaib Shekfeh, Srinivasaraghavan Kannan, Wolfgang Sippl and Manfred Jung
Med. Chem. Commun., 2012, 3, 305-311
DOI: 10.1039/C2MD00211F

Small-molecule inhibitors of dimeric transcription factors: Antagonism of protein–protein and protein–DNA interactions
Jeremy L. Yap, Jay Chauhan, Kwan-Young Jung, Lijia Chen, Edward V. Prochownik and Steven Fletcher
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00289B

Towards biocompatible nanovalves based on mesoporous silica nanoparticles
Ying-Wei Yang
Med. Chem. Commun., 2011, 2, 1033-1049
DOI: 10.1039/C1MD00158B

Molecular obesity, potency and other addictions in drug discovery
Michael M. Hann
Med. Chem. Commun., 2011, 2, 349-355
DOI: 10.1039/C1MD00017A

SAR mining and its application to the design of TRPA1 antagonists
James E. J. Mills, Alan D. Brown, Thomas Ryckmans, Duncan C. Miller, Sarah E. Skerratt, Carolyn M. Barker and Mark E. Bunnage
Med. Chem. Commun., 2012, 3, 174-178
DOI: 10.1039/C1MD00213A

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to MedChemComm? Then why not submit to us today or alternatively email us your suggestions.

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Review of the biosynthetic MEP pathway and potential anti-infective agents

Audrey Odom, Raman Sharma and colleagues present a review examining the enzymes in the biosynthetic non-mevalonate (MEP) pathway from a detailed medicinal chemistry and structural biology perspective. The MEP pathway is utilised by plants but is absent in mammalian systems, making it a very attractive target for the development of potential next generation antimicrobial chemotherapeutics as well as novel herbicides.

Want to find out more about this pathway and its potential agents? You’re just a click away….


The MEP pathway and the development of inhibitors as potential anti-infective agents
Ian Hale, Paul M. O’Neill, Neil G. Berry, Audrey Odom and Raman Sharma
Med. Chem. Commun., DOI: 10.1039/C2MD00298A

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Review article on small-molecule inhibitors of dimeric transcription factors: a challenging area

Disruption of protein–protein or protein–DNA interactions involved in transcriptional machinery using small molecules poses a real challenge owing to several factors, including: the large interfacial areas involved, the lack of obvious binding sites, and the large free energy of association between the interfaces.

However, in recent years there has been considerable success in the dimeric transcription factor disruption using small molecules. Steven Fletcher and co-workers at University of Maryland School of Pharmacy, provide a review of the progress made in this area since 2008.

This review covers:

  • Inhibitors of STAT3
  • Inhibitors of c-Myc
  • Inhibitors of AP-1
  • Inhibitors of HIF-1

Small-molecule inhibitors of dimeric transcription factors: Antagonism of protein–protein and protein–DNA interactions
Jeremy L. Yap, Jay Chauhan, Kwan-Young Jung, Lijia Chen, Edward V. Prochownik and Steven Fletcher
Med. Chem. Commun., 2012,
DOI: 10.1039/C2MD00289B, Review

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Top ten most accessed articles in January

This month sees the following articles in MedChemComm that are in the top ten most accessed:

Minisci reactions: Versatile CH-functionalizations for medicinal chemists
Matthew A. J. Duncton
Med. Chem. Commun., 2011, 2, 1135-1161
DOI: 10.1039/C1MD00134E

Antimalarial peroxides: advances in drug discovery and design
Rachel D. Slack, Alexander M. Jacobine and Gary H. Posner
Med. Chem. Commun., 2012, 3, 281-297
DOI: 10.1039/C2MD00277A

Structural enrichment of HTS compounds from available commercial libraries
Tetyana Petrova, Alexander Chuprina, Raman Parkesh and Alexei Pushechnikov
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00302C

Towards biocompatible nanovalves based on mesoporous silica nanoparticles
Ying-Wei Yang
Med. Chem. Commun., 2011, 2, 1033-1049
DOI: 10.1039/C1MD00158B

Polyamine-based small molecule epigenetic modulators
Shiv K. Sharma, Stuart Hazeldine, Michael L. Crowley, Allison Hanson, Ross Beattie, Sheeba Varghese, Thulani M. D. Senanayake, Aiko Hirata, Fusao Hirata, Yi Huang, Yu Wu, Nora Steinbergs, Tracey Murray-Stewart, Ian Bytheway, Robert A. Casero and Patrick M. Woster
Med. Chem. Commun., 2012, 3, 14-21
DOI: 10.1039/C1MD00220A

The discovery of novel 10,11-dihydro-5H-dibenz[b,f]azepine SIRT2 inhibitors
Paolo Di Fruscia, Ka-Kei Ho, Sasiwan Laohasinnarong, Mattaka Khongkow, Sebastian H. B. Kroll, Suhail A. Islam, Michael J. E. Sternberg, Karin Schmidtkunz, Manfred Jung, Eric W.-F. Lam and Matthew J. Fuchter
Med. Chem. Commun., 2012, 3, 373-378
DOI: 10.1039/C2MD00290F

The development of quinolone esters as novel antimalarial agents targeting the Plasmodium falciparum bc 1 protein complex
Robin Cowley, Suet Leung, Nicholas Fisher, Mohammed Al-Helal, Neil G. Berry, Alexandre S. Lawrenson, Raman Sharma, Alison E. Shone, Stephen A. Ward,  Giancarlo A. Biagini and Paul M. O′Neill
Med. Chem. Commun., 2012, 3, 39-44
DOI: 10.1039/C1MD00183C

A comparative analysis of the molecular topologies for drugs, clinical candidates, natural products, human metabolites and general bioactive compounds
Hongming Chen,  Ola Engkvist,  Niklas Blomberg and Jin Li
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00238H

Inhibitors of Stat5 protein signalling
Abbarna A. Cumaraswamy, Aleksandra Todic, Diana Resetca, Mark D. Minden and Patrick T. Gunning
Med. Chem. Commun., 2012, 3, 22-27
DOI: 10.1039/C1MD00175B

From the protein’s perspective: the benefits and challenges of protein structure-based pharmacophore modeling
Marijn P. A. Sanders, Ross McGuire, Luc Roumen, Iwan J. P. de Esch, Jacob de Vlieg, Jan P. G. Klomp and Chris de Graaf
Med. Chem. Commun., 2012, 3, 28-38
DOI: 10.1039/C1MD00210D

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to MedChemComm? Then why not submit to us today or alternatively email us your suggestions.

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Reviews on DNA methyltransferases, amphotericin B and antimalarial peroxides in Issue 3

On  the cover of this month’s issue is an image from Nadine Martinet et al. accompanying their review on small molecule inhibitors of DNA methyltransferases.  This article forms part of our recent Epigenetics collection, which also includes articles from Manfred Jung, Wolfgang Sippl, Antonello Mai and Stephen Frye.

Small molecules DNA methyltransferases inhibitors
Nadine Martinet, Benoît Y. Michel, Philippe Bertrand and Rachid Benhida
DOI: 10.1039/C1MD00194A

The issue also contains reviews from Peter Kovacic and Andrew Cooksy discussing the mechanism of the antifungal drug amphotericin B and Gary H. Posner et al. on recent advances in the design of cyclic peroxides for the treatment of malaria.

Novel, unifying mechanism for amphotericin B and other polyene drugs: electron affinity, radicals, electron transfer, autoxidation, toxicity, and antifungal action
Peter Kovacic and Andrew Cooksy
DOI: 10.1039/C2MD00267A

Antimalarial peroxides: advances in drug discovery and design
Rachel D. Slack, Alexander M. Jacobine and Gary H. Posner
DOI: 10.1039/C2MD00277A

View these and many other interesting articles online here

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Nominations now open – MedChemComm Emerging Investigator Lectureship

Nominations are now open for the 2012 MedChemComm Emerging Investigator Lectureship. This new, annual Lectureship is given to recognise an emerging scientist who has made a significant contribution to their research field.

Members of the community are welcome to make a nomination for the Lectureship. In order to make a nomination, please contact the MedChemComm Editorial Office with the name and affiliation of the nominee and a brief description of why they should be considered. In order to be eligible for the MedChemComm Emerging Investigator Lectureship, the candidate should have completed their PhD on or after 31st December 2001.

Nominations close on 31st March 2012

The recipient of the Lectureship will be asked to present a lecture at an international meeting. The MedChemComm Editorial Office will provide a contribution to the recipient for travel and accommodation costs. The recipient of the Lectureship will be selected by a panel comprised of MedChemComm Editorial Board members.

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Review article on β-lactams and β-lactone probes for chemical biology

β-lactams and β-lactone probes for chemical biologyThomas Böttcher and Stephan A. Sieber here review the use of β-lactams and β-lactones for activity-based protein profiling.  ABPP uses small molecules to target the active site of specific enzymes and is useful for understanding protein targets of natural products, drugs or synthetic libraries.   β-Lactams and β-lactones are ideal probes for ABPP due to their so-called ‘privileged structures’, i.e. they have a core scaffold that can be recognised by a wide range of enzyme classes and can be ‘fine-tuned to obtain customized target selectivity’.

Take a look at this detailed review, which provides an update to of the field of activity-based β-lactam and β-lactone probes and their applications in chemical biology:

β-Lactams and β-lactones as activity-based probes in chemical biology
Thomas Böttcher and Stephan A. Sieber
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00275B

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Top ten most accessed articles in December

This month sees the following articles in MedChemComm that are in the top ten most accessed:

Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space
Alexander Alex, David S. Millan, Manuel Perez, Florian Wakenhut and Gavin A. Whitlock
Med. Chem. Commun., 2011, 2, 669-674
DOI: 10.1039/C1MD00093D

Molecular obesity, potency and other addictions in drug discovery
Michael M. Hann
Med. Chem. Commun., 2011, 2, 349-355
DOI: 10.1039/C1MD00017A

Minisci reactions: Versatile CH-functionalizations for medicinal chemists
Matthew A. J. Duncton
Med. Chem. Commun., 2011, 2, 1135-1161
DOI: 10.1039/C1MD00134E

A comparative analysis of the molecular topologies for drugs, clinical candidates, natural products, human metabolites and general bioactive compounds
Hongming Chen,  Ola Engkvist,  Niklas Blomberg and Jin Li
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00238H

Towards biocompatible nanovalves based on mesoporous silica nanoparticles
Ying-Wei Yang
Med. Chem. Commun., 2011, 2, 1033-1049
DOI: 10.1039/C1MD00158B

Epigenetics — an emerging and highly promising source of new drug targets
Nessa Carey
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00264C

2-Anilinonicotinyl linked 1,3,4-oxadiazole derivatives: Synthesis, antitumour activity and inhibition of tubulin polymerization
Ahmed Kamal, Y. V. V. Srikanth, Thokhir B. Shaik, M. Naseer A. Khan, Md. Ashraf, M. Kashi Reddy, K. Anil Kumar and Shasi V. Kalivendi
Med. Chem. Commun., 2011, 2, 819-823
DOI: 10.1039/C0MD00177E

The discovery and profile of PF-0868087, a CNS-sparing histamine H3 receptor antagonist for the treatment of allergic rhinitis
Graham Lunn, Charles E. Mowbray, Wai L. S. Liu, Valerie M. Joynson, Tanya Hay and Michael Yeadon
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00276K

Synthesis and SAR of 2,4-diaminopyrimidines as potent c-jun N-terminal kinase inhibitors
Xinyi Song, Yuanjun He, Marcel Koenig, Youseung Shin, Romain Noel, Weimin Chen, Yuan Yuan Ling, Daniel Feurstein, Li Lin, Claudia H. Ruiz, Michael D. Cameron, Derek R. Duckett and Theodore M. Kamenecka
Med. Chem. Commun., 2012, 3, 238-243
DOI: 10.1039/C1MD00219H

Impact of ion class and time on oral drug molecular properties
Paul D. Leeson,  Stephen A. St-Gallay and Mark C. Wenlock
Med. Chem. Commun., 2011, 2, 91-105
DOI: 10.1039/C0MD00157K

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to MedChemComm? Then why not submit to us today or alternatively email us your suggestions.

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Building a nation of scientists

An interview with Goverdhan Mehta, former president of the International Council for Science

Goverdhan Mehta talks to Sheena Elliott and Elinor Richards about the progress of science in India and the challenges scientists face

Goverdhan Mehta is a researcher, specialising in organic synthesis. He has helped to build institutions in India – the Indian Institute of Technology, Kanpur, the University of Hyderabad, and the Indian Institute of Science, Bangalore. He was director of the Indian Institute of Science (1998-2005) and vice chancellor of the University of Hyderabad (1994-1998).

Your research is focused on organic chemistry. What attracted you to that field?

There is something intrinsically fascinating about organic chemistry. In my early high school years, when I was exposed to interesting chemical structures, I was attracted to them. I had a sense of appreciation for art and organic molecules to me provided a wonderful expression of art at a molecular level.

What are your main achievements in the field?

I have worked in many areas of organic chemistry, but it’s synthesis that’s given me the greatest pleasure. As organic chemistry advanced, different contemporary challenges came to my attention. The main driver for me to pursue those challenges was the intricacy of the target structure synthesis. There was also an element of expectation that perhaps our research might become useful to society. We continue to need new drugs for a variety of disorders, so we synthesised a large number of natural products; many of them are biologically active and it is quite possible that some of them can provide leads for new drug discovery.

Over the last few years, I have become interested in how to address a problem that the ageing population is facing – neurodegeneration. It has been shown that some natural products can slow down neurodegeneration. In some cases, there is also an indication that they can help restore lost cognitive function. So I have been working on the synthesis of such lead molecules. As I’m getting older, I recognise the need for doing something in that area!

You’ve won numerous awards. Which achievements are you most proud of?

I don’t think that awards and recognition have necessarily brought me a great sense of joy. They do bring a sense of satisfaction because your peers have recognised your work. But I don’t think any serious researcher works for awards. It is the sheer joy of research that keeps people going. Recognition has come my way, but don’t think that I can equate that with the joy of doing research.

What are the challenges facing scientists in India and how could these be overcome?

Scientists all over the world are facing challenges on two fronts. The first problem is that scientists are not being supported by society as much as they should and some governments are not always forthcoming in terms of providing budgetary support. The second problem is that scientists, and science in general, have become isolated both in terms of discipline and, to some extent, in terms of geographical location. This is being redressed now with increasing international collaborations, so in the geographical sense, the isolation is being reduced. But I think disciplinary isolation vis a vis other knowledge streams and fragmentation of science is still a serious challenge.

It is a good time for scientists in India because the government is very supportive of science. Funding is no longer as serious a problem as it is in other parts of the world. Recently, our prime minister said that the budget for science will be almost doubled over the next few years. But I’m not too sure that we as a scientific community are steering science in India in the direction that it ought to be heading. I believe that the government and the scientific community must set a goal that in the next 10 years, India will be among the world’s leading scientific countries.

What is your opinion on the perception that Indian science and research is falling behind the rest of the world, following recent comments by Prime Minister Manmohan Singh?

Prime Minister Singh’s statement referred mainly to China. China has made more progress in science and technology than India. Scientific productivity in India has increased, but not as much as in China. Since we are behind, to simply say that we are walking and walking well is not enough. We should be galloping to catch up. My judgement is that our progress is not commensurate with the support that the government is providing, and not commensurate with the capacity, capability, enthusiasm and the vibrancy that our youth have. We can achieve much more.

How do the different industries compare (the pharmaceutical industry in particular or the more general chemical industry)?

It is only over the last 10 or 12 years, since the economic reforms, that industry in India has grown at such a rate so as to be in a position to invest in research and development. I expect that investment by industry is going to rise; however, the current level of investment is not in an acceptable range. There are certain sectors – pharma, for example – and some other chemical industries, where I think India’s potential is immense, but there are some challenges with the policies that are being pursued. We have to devise a well thought out strategy.

The prime minister’s Science Advisory Council reported that there in an absence of any Indian universities among the world’s best. What is your opinion on the quality of universities in India?

I’m not a great believer in the ranking systems being followed, but the fact is that no Indian university features among the top few hundred  universities. However, if we were to look at undergraduate teaching, India has institutions that produce graduates through excellent teaching and training. The graduates are probably as good as they are anywhere else in the world. If you were to grade an institution on the quality of undergraduates, I would say that the Indian Institutes of Technology rank among the top 10 institutions in the world. But, if you bring in research and other elements, they will not feature anywhere near the top. So the quality of research is a serious problem. I think it is high time that the scientific community and scientific leadership in our country sort out an effective, implementable strategy to make a major shift.

You experienced difficulty obtaining a visa to travel to the US in 2006, when you were invited to give a lecture at the University of Florida. At the time, a report from the National Academy of Sciences in the US said that at least 3000 scientists had faced a similar problem. Have things improved since then or do you believe that the visa problem is hampering scientific progress and career development for scientists?

It was ironic that I and a leading scientist from the US, Jane Lubchenco (who at that time was president of the International Council for Science before I succeeded her), wrote an editorial about the principle of universatility of science and the visa regime in Science a few months before this happened. We wrote that it was important for the international growth of science that scientists were able to travel. Little did I realise that soon I would be a victim of this! I think the situation has improved, but a lot more needs to be done. While the US National Academy of Sciences is playing a very positive role towards this end, the academies can only do the advocacy. Eventually, it is the government and the state department of security staff that makes the final judgement.

If you have any spare time, how do you fill it?

For most scientists, and I’m no exception, your research is a hobby. What other profession can give you that pleasure and privilege? In a previous interview, I was asked what I would wish for. I said we Indians believe in rebirth and so the only wish I have is that if I were to be born again, I would be a scientist. I would like to be a chemist, hopefully a better one.

Read some of Goverdhan Mehta’s recent research:

Towards a temperature-guided molecular switch: an unusual reversible low-temperature polymorphic phase transition in a conformationally locked environment
Goverdhan Mehta and Saikat Sen, Chem. Commun., 2009, 5981
DOI: 10.1039/b905651c

Understanding the self-assembling process in crystalline cyclooctitols: an insight into the conformational flexibility of medium-sized rings
Goverdhan Mehta, Saikat Sen and Kotapalli Pallavi, CrystEngComm, 2008, 10, 534
DOI: 10.1039/b712877k

Additive induced polymorphous behavior of a conformationally locked hexol
Goverdhan Mehta, Saikat Sen and Kailasam Venkatesan, CrystEngComm, 2007, 9, 144
DOI: 10.1039/b613949c

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A new generation of tuberculosis drugs

Scientists in India are targeting enzymes responsible for catalysing the formation of bonds to repair nicks in the phosphodiester backbone of DNA – called DNA ligases – to tackle the ever-growing health concern of multi-drug resistant bacteria, in particular against tuberculosis.

Tuberculosis bacteria

Unlike current drugs, the new compound targets just the bacterial enzymes instead of both bacterial and human enzymes

DNA ligases use either adenosine triphosphate (ATP) or nicotinamide adenine dinucleotide (NAD+) as cofactors (small molecules that help promote biological reactions) in cellular processes, such as DNA repair and replication. Humans only have the DNA ligases that utilise ATP, but bacteria use both. Studies have shown that NAD+-dependent ligase is indispensable in several bacterial, including Mycobacterium tuberculosis and Escherichia coli, making them attractive drug targets.

The team from the Central Drug Research Institute in Lucknow synthesised and screened drugs from aryl hydroxamates to show that they were active against bacterial, but not human, versions of DNA ligase, as well as concluding that they did not have any general DNA interactions.

‘Hydroxamates offer a better chance to develop new economical anti-tuberculosis drugs. The ease of synthesis makes them attractive,’ says Rama Pati Tripathi, part of the team in Lucknow.

‘Developing new small molecule compounds that are able to distinguish between ATP- and NAD+-dependent ligases, such as the compounds presented here, is important for engineering molecules with increased levels of specificity,’ says Rommie Amaro, an expert on enzymological and drug discovery studies at the University of California, Irvine, US. ‘Such specificity is critical for these compounds to be useful from a clinical perspective.’ He adds that the work could help develop compounds that are active against RNA editing ligases. These are potential antiparasitic targets for several of the world’s most devastating diseases, such as Chagas disease and African sleeping sickness.

Synthesis and bioevaluation of aryl hydroxamates distinguishing between NAD+ and ATP-dependent DNA ligases
Vandna Kukshal, Mridul Mishra, Arya Ajay, Taran Khanam, Rahul Sharma, Divya Dube, Deepti Chopra, Rama Pati Tripathi and Ravishankar Ramachandran
DOI: 10.1039/C2MD00168C

Read the original article at Chemistry World

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